A bone-resorption surface-targeting nanoparticle to deliver anti-miR214 for osteoporosis therapy

Cai, Meili; Yang, Li; Zhang, Shufan; Liu, Jiafan; Sun, Yao; Wang, Xiaogang

doi:10.2147/ijn.s139775

Cited by 50 publications

(42 citation statements)

References 67 publications

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“…In addition, osteoclast-related genes were also down-regulated, such as TRAP and CTSK. 41 In addition, a recent study reported that miR-142-5p was also involved in the efficient regulation of osteoclast differentiation through targeting PTEN. And miR-142-5p regulated osteoclast differentiation through PTEN/PI3K/AKT/ FoxO1 pathway.…”

Section: Discussionmentioning

confidence: 99%

<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

Zhao¹,

Liu²,

Xie³

et al. 2020

OTT

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Osteoclastogenesis is a key process in osteolytic bone metastasis (BM). Previous studies indicated that some miRNAs could regulate cancers progression and osteoclastogenesis. Our purpose was to investigate the roles of lung cancer cells-derived circulating miR-21 on osteoclastogenesis and its clinical significance in BM patients. Materials and Methods: The difference of miRNA expression in two lung cancer cell lines SBC-5 (with characteristic BM ability) and SBC-3 (without BM ability) were analyzed by microarray and qRT-PCR. Circulating miR-21 levels of lung cancer patients with or without BM were compared by qRT-PCR. The TRAP staining was used to investigate the effects of conditioned media from lung cancer cell lines or patients' plasma with different miR-21 levels on osteoclastogenesis. ROC curve was used to evaluate the diagnostic performance of circulating miR-21 in BM patients. Results: We found that miR-21 expression was specifically higher in SBC-5 than that in SBC-3 cells. The supernatants of SBC-5 cells with higher-level miR-21 promoted osteoclastogenesis. Moreover, we demonstrated that the circulating miR-21 level was significantly higher in BM patients than that in non-BM patients. The plasma from BM patients with higher-level miR-21 could also promote osteoclastogenesis. Mechanistically, lung cancer cells-derived circulating miR-21 could be transferred into osteoclast precursor cells and promote osteoclastogenesis probably by inhibiting PTEN. Finally, clinical data showed that circulating miR-21 had a potential for the diagnosis of BM. Conclusion: Overall, our findings suggested that circulating miR-21 played important roles in osteoclastogenesis of lung cancer patients and may serve as a biomarker to diagnose BM of lung cancer.

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Section: Discussionmentioning

confidence: 99%

<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

Zhao¹,

Liu²,

Xie³

et al. 2020

OTT

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“…Nanoparticles also facilitate the delivery of miRNA‐based gene therapy in osteoporosis treatment. In a study by Cai et al., polyurethane nanomicelles encapsulating anti‐miR214 was injected in ovariectomized mice . Without overt toxicity or eliciting an immune response, this delivery system successfully delivered the anti‐miR214 to surface of osteoclasts and inhibited their differentiation.…”

Section: Current Osteoporosis Treatmentmentioning

confidence: 99%

“…In a study by Cai et al, polyurethane nanomicelles encapsulating anti-miR214 was injected in ovariectomized mice. 205 Without overt toxicity or eliciting an immune response, this delivery system successfully delivered the anti-miR214 to surface of osteoclasts and inhibited their differentiation. Elevated miR-214 levels have been correlated with lower bone formation in bone specimens from aged patients.…”

Section: Nanomedicines For Osteoporosismentioning

confidence: 99%

The underlying pathophysiology and therapeutic approaches for osteoporosis

Awasthi

Mani

Singh

et al. 2018

Medicinal Research Reviews

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With an increase in the ageing population worldwide, the prevalence of osteoporosis increases at an alarming rate in both male and female irrespective of their ethnicity. At present, the currently available therapeutic options are mostly limited to either bone resorptive or bone forming efficacies and both approaches are associated with serious side effects. Despite these options, there is still need for newer therapeutics to treat osteoporosis, which can offer beneficial effects for maintaining balanced dynamics between bone formation and bone resorption, devoid of any side effect. The proper understanding of pathophysiology of the disease is essential for designing or investigating an effective and safe anti-osteoporotic agent. This review represents a discussion around the molecular targets with their implications in disease progression, available therapeutic options, the emerging targets, and the importance of designing an effective anti-osteoporotic agent.

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“…(10)(11)(12)(13)(14) A recent study has shown in vivo injection of anti-miR-214-induced improvement of bone microarchitecture and bone mass in mice. (15) Other reports also suggest an association between the serum levels of some miRNAs with human osteoporosis. (16)(17)(18)(19)(20) Seeliger and colleagues reported miR-21, miR-23a, miR-24, miR-25, miR-100, and miR-125b to be significantly higher in the serum of patients with osteoporosis than healthy individuals.…”

Section: Introductionmentioning

confidence: 98%

Lack of Association Between Select Circulating miRNAs and Bone Mass, Turnover, and Fractures: Data From the OFELY Cohort

Feurer

Kan

Croset

et al. 2019

Journal of Bone and Mineral Research

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Postmenopausal osteoporosis is characterized by the occurrence of fragility fracture with an increase in morbidity and mortality. Recently, microRNAs (miRNAs) have raised interest as regulators of translational repression, mediating a number of key processes, including bone tissue in both physiological and diseased states. The aim of this study was to examine the serum levels of 32 preselected miRNAs with reported function in bone and their association with osteoporotic fracture. We performed cross-sectional and longitudinal analyses from the OFELY Cohort. Serum levels of the miRNAs were quantified by qRT-PCR in 682 women: 99 premenopausal and 583 postmenopausal women, with 1 and 122 women with prevalent fragility fractures in each group, respectively. We have collected clinical variables (such as age, prevalent, and incident fractures), bone turnover markers (BTMs), BMD by dual X-ray absorptiometry, and bone microarchitecture with HRpQCT. We observed a number of miRNAs to be associated with fragility fractures (prevalent or incident), BTMs, BMD, and microarchitecture. This effect, however, was negated after age adjustment. This may be because age was also strongly associated with the serum levels of the 32 miRNAs (correlation coefficient up to 0.49), confirming previous findings. In conclusion, in a well-characterized prospective cohort with a sizeable sample size, we found no evidence that these 32 preselected miRNAs were not associated with BTMs, BMD, microarchitecture, and or fragility fractures. Ã CTX, mg/L (min-max) 0.466 (0.057-1.470) 0.374 (0.107-1.030) 0.481 (0.057-1.470) Ã Osteocalcin, ng/mL (min-max) Ã Ã p value considered as significant if <0.05. Tt.vBMD ¼ total volumetric bone mineral density; Ct.vBMD ¼ cortical volumetric bone mineral density; Tb.vBMD ¼ trabecular volumetric bone mineral density; BAP ¼ bone alkaline phosphatase. Journal of Bone and Mineral Research LACK OF ASSOCIATION BETWEEN miRNAs AND BONE: DATA FROM THE OFELY COHORT 5 FEURER ET AL. Ã Radius Tt.vBMD, mg/cm 3 (min-max) 245.6 (122.9-482.1) 278.1 (101.9-515.8) Ã Radius Ct.vBMD, mg/cm 3 (min-max) 771.9 (556.9-956.4) 803.0 (572.6-1004.8) Ã Radius Tb.vBMD, mg/cm 3 (min-max) 123.2 (50.3-264.0) 141.8 (17.5-262.8) Ã Tibia Tt.vBMD, mg/cm 3 (min-max) 228.3 (124.2-371.2) 252.8 (109.0-417.4) Ã Tibia Ct.vBMD, mg/cm 3 (min-max) 702.6 (437.7-912.7) 744.6 (376.7-976.6) Ã Tibia Tb.vBMD, mg/cm 3 (min-max) 133.6 (52.0-212.6) 149.3 (31.9-254.7) Ã CTX, mg/L (min-max) 0.463 (0.057-1.16) 0.484 (0.062-1.470) NS Osteocalcin, ng/mL (min-max) 28.6 (4.2-90.2) 27.7 (6.5-86.2) NS P1NP, ng/mL (min-max) 49.0 (8.1-138.6) 21.5 (10.0-139.7) NS BAP, UI/L (min-max) 39.3 (15.2-69.4) 38.8 (10.1-88.6) NS Ã p-value considered as significant if <0.05. Tt.vBMD ¼ total volumetric bone mineral density; Ct.vBMD ¼ cortical volumetric bone mineral density; Tb.vBMD ¼ trabecular volumetric bone mineral density; BAP ¼ bone alkaline phosphatase. 8 FEURER ET AL.

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A bone-resorption surface-targeting nanoparticle to deliver anti-miR214 for osteoporosis therapy

Cited by 50 publications

References 67 publications

<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

The underlying pathophysiology and therapeutic approaches for osteoporosis

Lack of Association Between Select Circulating miRNAs and Bone Mass, Turnover, and Fractures: Data From the OFELY Cohort

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